4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency? - Full Text View

Sponsor:	University of Florida
Collaborators:	Alpha-1 Foundation Brantly, Mark L., M.D.
Information provided by (Responsible Party):	University of Florida
ClinicalTrials.gov Identifier:	NCT00067756

Purpose

The purpose of this study is to find out whether 4-PBA will increase the level of AAT in persons with AAT deficiency whether or not they have liver disease.

Condition	Intervention	Phase
Alpha 1-Antitrypsin Deficiency	Drug: 4 Phenyl Butyrate (4PBA)	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	"4 Phenyl Butyrate Mediated Secretion Rescue in Alpha 1-Antitrypsin Deficient Individuals"

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-1 antitrypsin deficiency

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency Liver Diseases

Drug Information available for: Sodium phenylbutyrate

U.S. FDA Resources

Further study details as provided by University of Florida:

Primary Outcome Measures:

To determine if 4-PBA significantly increases secretion of AAT in AAT-deficient individuals with and without liver disease. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the pharmacokinetics of 4-PBA [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Enrollment:	12
Study Start Date:	November 2001
Study Completion Date:	October 2003
Primary Completion Date:	October 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 4-PBA The study will involve a dose escalation and pharmacokinetics component The study group will be comprised of a total of 10 patients equally divided into PiZZ* AAT-deficient individuals with (n=5) and without (n=5) clinical evidence of mild to moderate hepatocellular injury.	Drug: 4 Phenyl Butyrate (4PBA) During the first 3 days of this phase baseline serum AAT levels will be determined. The participants will be then given increased amounts of 4-PBA orally in 6 divided doses (day 4-6, 30 g/day and day 7-9, 40/day Other Name: 4-phenyl butyric acid

Detailed Description:

The purpose of this study is to determine whether 4-PBA will significantly increase serum Z AAT levels in AAT-deficient individuals with and without evidence of hepatocellular injury and to assess its effects on liver injury.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-65
Serum A1-PI levels <11uM an appropriate genetic phenotype/genotype
5 of 10 subjects must have documented laboratory evidence of liver disease
Willingness to withhold Prolastin therapy for 6 weeks prior to screening and throughout the 4-PBA dosing period (up to 3 months)

Exclusion Criteria:

Any cause of liver disease other than Alpha-1 Antitrypsin deficiency
Evidence of advanced liver disease
HIV positive
Use of systemic steroids, ursodeoxycholic acid (Actigall, Urso), or herbs in the prior 6 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00067756

Locations

United States, Florida
University of Florida
Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

Alpha-1 Foundation

Brantly, Mark L., M.D.

Investigators

Principal Investigator:

Mark L Brantly, MD

University of Florida

More Information

Additional Information:

Alpha-1 Foundation Alpha-1 Research Program This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Florida
ClinicalTrials.gov Identifier:	NCT00067756 History of Changes
Other Study ID Numbers:	87-2001
Study First Received:	August 26, 2003
Last Updated:	September 16, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Florida:

Pulmonary Disease
Liver Disease

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Butyric Acid
4-phenylbutyric acid

Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012